The main thrust of this project is to develop experimental approaches to the study of leukemia founded on immunogenetic principles that may be helpful in achieving progress toward the control or elimination of leukemias in man. Four interrelated systems will be investigated: (1) with respect to the role of H-2 linked immune response genes in control of neoplastic cell growth in AKR leukemogenesis we shall study (a) the role of suppression, (b) the role and response to a 58K protein on the cell surface of some AKR tumor cells (BW5147) and (c) the possibility of vaccination against spontaneous leukemia. (2) With respect to the existence of a transformation-sensitive lymphocyte population (TSL) our goal is to determine (a) whether such a population is identifiable by a new cell surface marker, Ly 9.2 (or its counterpart Ly 9.1) (b) the pathway of differentiatin of Ly 9.2 positive cells, (c) and the outcome of elimination of Ly 9.2 positive cells on susceptibility to leukemia. In addition, (d) we seek to chemically characterize Ly 9.1 or 2 antigens and determine their genetic and chemical polymorphism. (3) With respect to question of a viral etiology for x-irradiation-induced leukemia we wish to further determine the role of H-2D linked genes in (a) alterations of bone-marrow thymocyte differentiation pathways and (b) in immune surveillance against neoplasia. (4) With regard to the immunology of resistance to RadLV-induced neoplasia we wish to (a) characterize the effector cells involved (b) determine the role of suppression during the disease, and (c) in addition, a provocative question raised by our observations regarding effects of RadLV infection on H-2 antigen expression is the role of viral integration at or near H-2D gene(s). To this end, we shall examine amino acid homologies between H-2D antigens and viral proteins, particularly p12.